R-Ras regulates β1-integrin trafficking via effects on membrane ruffling and endocytosis

摘要: Integrin-mediated cell adhesion and spreading is dramatically enhanced by activation of the small GTPase, R-Ras. Moreover, R-Ras localizes to leading edge migrating cells, regulates membrane protrusion. The exact mechanisms which integrin function are not fully known. Nor much known about spatiotemporal relationship between these two molecules, an understanding may provide insight into regulation integrins. GFP-R-Ras localized plasma membrane, most specifically in ruffles, Cos-7 cells. was endocytosed from trafficked via multiple pathways, one involved large, acidic vesicles that were positive for Rab11. Cells transfected with a dominant negative form did had decreased spreading, contained numerous, non-trafficking vesicles. Conversely, cells constitutively active greater number ruffles large compared wild-type Ruffle formation inhibited knock-down endogenous siRNA, suggesting activated just component of, but also architect ruffle formation. Importantly, β1-integrin co-localized Expression or knock down siRNA prevented accumulation impaired endocytosis β1-integrin, β1-integrin-mediated adhesion. Knock-down perturbed dynamics another membrane-localized protein, GFP-VSVG, more global role on dynamics. However, while co-internalized integrins, it traffic VSVG, instead moved laterally out within plane levels Our results suggest involves trafficking cycle protrusion, ruffling, regulated R-Ras, providing novel mechanism integrins linked through control